Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • University of Münster
  • Julius Maximilian University of Würzburg
  • Washington University School of Medicine
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)e1007671
TidskriftPLoS Pathogens
Volym15
Utgåva nummer6
StatusPublished - 2019 jun
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Ines Ambite, 2019, Lund: Lund University: Faculty of Medicine. 87 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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